JPH3 Facilitates Cisplatin Resistance in Anaplastic Thyroid Cancer via Activation of the JAK-STAT Signaling Pathway.

BACKGROUND: Junctophilin 3 (JPH3) acts as a tumor suppressor in several cancers; however, the role of JPH3 in anaplastic thyroid cancer (ATC) is still unknown.

METHODS: Via bioinformatics prediction and verified through Western blot experiments, the expression level of JPH3 in ATC was ascertained. Subsequently, the role of JPH3 in ATC cells was validated via in vitro and in vivo experiments, and the molecular mechanism of JPH3 in ATC was further illuminated. Eventually, the mechanism of JPH3 on cisplatin (DDP)-resistant ATC cells was probed. The results indicated that JPH3 was highly expressed in thyroid cancer (TC), and the survival period of patients with high expression was significantly curtailed.

RESULTS: JPH3 was upregulated in TC tissues compared with the normal thyroid tissues. Our experiments disclosed that JPH3 acted as an oncogene in ATC cells, facilitating tumor development, and JPH3 can activate the JAK-STAT signaling pathway by upregulation of collagen type XXVI alpha 1 chain (COL26A1), and experiments attested that JPH3 promoted the proliferation, invasion, and migration of ATC cells by activating the JAK-STAT signaling pathway. Further research uncovered that JPH3 was also involved in the process of DDP resistance in ATC cells. By activating the JAK-STAT signaling pathway, JPH3 induced the malignant phenotype of DDP-resistant ATC cells.

CONCLUSIONS: JPH3 functions as a potent oncogenic driver in ATC, promoting tumor proliferation, invasion, and migration through the activation of the JAK-STAT signaling pathway. This oncoprotein contributes to enhanced DDP resistance in ATC cells via JAK-STAT-mediated mechanisms, offering novel insights into the molecular basis of chemoresistance in this highly aggressive malignancy.